Our laboratory has been concerned with three interrelated areas of human immunobiology: (1) the identification of receptors and differentiation antigens on human lymphocytes, (2) the development of techniques for the isolation of lymphocyte subclasses. and, (3) the in vitro analysis of immunologic functions within isolated subclasses. Recently, we have identified differentiation antigens on human thymocytes and subclasses of peripheral T cells using both heteroantisera and alloantisera. Heteroantibodies directed against peripheral T cell differentiation antigens were prepared by immunization of rabbits with highly purified T cells and rendered specific by absorption with autologous B cell lines. The resulting sera recognizes antigens which distinguish the subclass of T cells (TH1 plus) responsible for MLC response, mediator production and helper activity. In contrast, T cells not bearing the TH1 antigen do not mediate TH1 plus functions, but proliferate in response to soluble antigens and suppress B cell differentiation. Moreover, we have observed that alloantisera present in some patients with autoimmune diseases distinguish functionally distinct T cell subclasses. Our goals are to: (1) continue to identify heteroantisera and alloantisera which distinguish subclasses of T cells. (2) Isolate (by column immunoabsorbent and rosette techniques) and functionally characterize T cell subclasses with respect to MLC response; mediator production, regulation of B cell differentiation and the generation of cytotoxic cells, (3) characterize antigens detected by alloantisera and determine their role in immune functions and, (4) apply the analysis of T cell subclasses to the direct study of immune abnormalities in patients.